87782 Federal Register / Vol. 88, No. 242 / Tuesday, December 19, 2023 / Notices 

definitively shown that the result is 

due to interference with vitamin K 

metabolism, e.g., salicylates 

MEPHYTON (phytonadione) tablets, 5 

mg, are currently listed in the 

‘‘Discontinued Drug Product List’’ 

section of the Orange Book. 

Lachman Consults submitted a citizen 

petition dated October 17, 2023 (Docket 

No. FDA–2023–P–4596), under 21 CFR 

10.30, requesting that the Agency 

determine whether MEPHYTON 

(phytonadione) tablets, 5 mg, were 

withdrawn from sale for reasons of 

safety or effectiveness. 

After considering the citizen petition 

and reviewing Agency records and 

based on the information we have at this 

time, FDA has determined under 

§ 314.161 that MEPHYTON 

(phytonadione) tablets, 5 mg, were not 

withdrawn for reasons of safety or 

effectiveness. The petitioner has 

identified no data or other information 

suggesting that MEPHYTON 

(phytonadione) tablets, 5 mg, were 

withdrawn for reasons of safety or 

effectiveness. We have carefully 

reviewed our files for records 

concerning the withdrawal of 

MEPHYTON (phytonadione) tablets, 5 

mg, from sale. We have also 

independently evaluated relevant 

literature and data for possible 

postmarketing adverse events. We have 

found no information that would 

indicate that this drug product was 

withdrawn from sale for reasons of 

safety or effectiveness. 

Accordingly, the Agency will 

continue to list MEPHYTON 

(phytonadione) tablets, 5 mg, in the 

‘‘Discontinued Drug Product List’’ 

section of the Orange Book. The 

‘‘Discontinued Drug Product List’’ 

delineates, among other items, drug 

products that have been discontinued 

from marketing for reasons other than 

safety or effectiveness. FDA will not 

begin procedures to withdraw approval 

of approved ANDAs that refer to this 

drug product. Additional ANDAs for 

this drug product may also be approved 

by the Agency as long as they meet all 

other legal and regulatory requirements 

for the approval of ANDAs. If FDA 

determines that labeling for this drug 

product should be revised to meet 

current standards, the Agency will 

advise ANDA applicants to submit such 

labeling. 

Dated: December 14, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–27858 Filed 12–18–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–D–4395] 

Use of Real-World Evidence To 

Support Regulatory Decision-Making 

for Medical Devices, Draft Guidance for 

Industry and Food and Drug 

Administration Staff; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of the draft 

guidance entitled ‘‘Use of Real-World 

Evidence to Support Regulatory 

Decision-Making for Medical Devices.’’ 

FDA is issuing this draft guidance to 

clarify how FDA evaluates real-world 

data (RWD) to determine whether they 

are of sufficient quality for generating 

real-world evidence (RWE) that can be 

used in FDA regulatory decision-making 

for medical devices. This draft guidance 

proposes expanded recommendations to 

the 2017 guidance entitled ‘‘Use of RealWorld Evidence to Support Regulatory 

Decision-Making for Medical Devices.’’ 

This draft guidance is not final nor is it 

for implementation at this time. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by February 20, 2024 to ensure that the 

Agency considers your comment on this 

draft guidance before it begins work on 

the final version of the guidance. 

ADDRESSES: You may submit comments 

on any guidance at any time as follows: 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

comment will be made public, you are 

solely responsible for ensuring that your 

comment does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

comments, that information will be 

posted on https://www.regulations.gov. 

• If you want to submit a comment 

with confidential information that you 

do not wish to be made available to the 

public, submit the comment as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

Submit written/paper submissions as 

follows: 

• Mail/Hand Delivery/Courier (for 

written/paper submissions): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, FDA will post your comment, as 

well as any attachments, except for 

information submitted, marked and 

identified, as confidential, if submitted 

as detailed in ‘‘Instructions.’’ 

Instructions: All submissions received 

must include the Docket No. FDA– 

2023–D–4395 for ‘‘Use of Real-World 

Evidence to Support Regulatory 

Decision-Making for Medical Devices.’’ 

Received comments will be placed in 

the docket and, except for those 

submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 

https://www.regulations.gov or at the 

Dockets Management Staff between 9 

a.m. and 4 p.m., Monday through 

Friday, 240–402–7500. 

• Confidential Submissions—To 

submit a comment with confidential 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 88, No. 242 / Tuesday, December 19, 2023 / Notices 87783 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

An electronic copy of the guidance 

document is available for download 

from the internet. See the 

SUPPLEMENTARY INFORMATION section for 

information on electronic access to the 

guidance. Submit written requests for a 

single hard copy of the draft guidance 

document entitled ‘‘Use of Real-World 

Evidence to Support Regulatory 

Decision-Making for Medical Devices’’ 

to the Office of Policy, Center for 

Devices and Radiological Health, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 66, Rm. 5431, 

Silver Spring, MD 20993–0002; or to 

Office of Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

request. 

FOR FURTHER INFORMATION CONTACT: 

Soma Kalb, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 318, Silver Spring, 

MD 20993–0002, 301–796–6359; or 

James Myers, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 7301, 

Silver Spring, MD 20993, 240–402– 

7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is issuing this draft guidance to 

clarify how FDA evaluates RWD to 

determine whether they are of sufficient 

quality for generating RWE that can be 

used in FDA regulatory decision-making 

for medical devices. This draft guidance 

proposes expanded recommendations to 

the 2017 guidance entitled ‘‘Use of RealWorld Evidence to Support Regulatory 

Decision-Making for Medical Devices’’ 

(the 2017 RWE Guidance). On December 

29, 2022, the Food and Drug Omnibus 

Reform Act of 2022 (FDORA) was 

signed into law as part of the 

Consolidated Appropriations Act, 2023 

(Pub. L. 117–328). Section 3629 of 

FDORA ‘‘Facilitating the Use of Real 

World Evidence’’ directs FDA to issue 

or revise existing guidance on 

considerations for the use of RWD and 

RWE to support regulatory decision 

making. FDA is issuing this draft 

guidance to propose revisions to the 

2017 RWE Guidance to satisfy the 

requirement under section 3629(a)(2). 

This draft guidance also fulfills a 

commitment in section V.F. of the 

Medical Device User Fee Amendments 

Performance Goals and Procedures, 

Fiscal Years 2023 Through 2027 

(MDUFA V). 

This draft guidance includes FDA’s 

recommendations and considerations on 

the factors that are expected to be 

assessed to demonstrate whether the 

RWD are fit-for-purpose for a particular 

regulatory decision relating to medical 

devices. When this draft guidance is 

finalized, these recommendations and 

considerations will apply regardless of 

the RWD source and will encompass 

processes for conducting studies to 

generate RWE. A fit-for-purpose 

assessment should evaluate both the 

relevance and reliability of a RWD 

source, as discussed in more detail in 

the draft guidance. FDA recognizes that 

there may be other approaches to 

address the considerations identified in 

this draft guidance. We encourage 

sponsors to discuss their approach with 

FDA, especially if the approach diverges 

from the recommendations in this draft 

guidance, when finalized. 

The topics covered within this draft 

guidance are framed specifically for the 

use of RWD/RWE in regulatory 

submissions. This draft guidance 

includes additional clarity regarding the 

recommended methodologies for 

collection and analysis of RWD to 

generate RWE, and provides updated 

examples on previously used and 

accepted methodologies. This draft 

guidance also provides additional 

clarity regarding the use of clinical data 

collected from the use of a device 

authorized under an Emergency Use 

Authorization (EUA) and to describe the 

type of information that could be 

applicable to support a determination 

under the Clinical Laboratory 

Improvement Amendments (CLIA) (e.g., 

Waiver by Application). 

FDA recognizes and anticipates that 

the Agency and industry may need up 

to 60 days to perform activities to 

operationalize the recommendations 

within the final guidance. At this time, 

the Agency anticipates that, for 

regulatory submissions that will be 

currently pending with FDA after 

publication of the final guidance, as 

well as those submissions received 

within 60 days following publication of 

the final guidance, FDA generally would 

not anticipate that sponsors will be 

ready to include the newly 

recommended information outlined in 

the final guidance in their submission. 

FDA, however, would intend to review 

any such information if submitted at 

any time. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Use of Real-World Evidence to 

Support Regulatory Decision-Making for 

Medical Devices.’’ It does not establish 

any rights for any person and is not 

binding on FDA or the public. You can 

use an alternative approach if it satisfies 

the requirements of the applicable 

statutes and regulations. 

II. Electronic Access 

Persons interested in obtaining a copy 

of the draft guidance may do so by 

downloading an electronic copy from 

the internet. A search capability for all 

Center for Devices and Radiological 

Health guidance documents is available 

at https://www.fda.gov/medical-devices/ 

device-advice-comprehensiveregulatory-assistance/guidancedocuments-medical-devices-andradiation-emitting-products. This 

guidance document is also available at 

https://www.regulations.gov, https://

www.fda.gov/regulatory-information/ 

search-fda-guidance-documents or 

https://www.fda.gov/vaccines-bloodbiologics/guidance-complianceregulatory-information-biologics. 

Persons unable to download an 

electronic copy of ‘‘Use of Real-World 

Evidence to Support Regulatory 

Decision-Making for Medical Devices’’ 

may send an email request to CDRHGuidance@fda.hhs.gov to receive an 

electronic copy of the document. Please 

use the document number GUI00500012 

and complete title to identify the 

guidance you are requesting. 

III. Paperwork Reduction Act of 1995 

While this guidance contains no new 

collection of information, it does refer to 

previously approved FDA collections of 

information. The previously approved 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act (44 U.S.C. 3501–3521). 

The collections of information in the 

following table have been approved by 

OMB: 


lotter on DSK11XQN23PROD with NOTICES1
87784 Federal Register / Vol. 88, No. 242 / Tuesday, December 19, 2023 / Notices 

21 CFR part or guidance Topic OMB control 

No. 

807, subpart E ............................................................................ Premarket notification ................................................................ 0910–0120 

814, subparts A through E .......................................................... Premarket approval .................................................................... 0910–0231 

814, subpart H ............................................................................ Humanitarian Use Devices; Humanitarian Device Exemption .. 0910–0332 

812 .............................................................................................. Investigational Device Exemption .............................................. 0910–0078 

860, subpart D ............................................................................ De Novo classification process .................................................. 0910–0844 

‘‘Requests for Feedback and Meetings for Medical Device 

Submissions: The Q-Submission Program’’.

Q-Submissions and Early Payor Feedback Request Programs 

for Medical Devices.

0910–0756 

822 .............................................................................................. Postmarket Surveillance of Medical Devices ............................ 0910–0449 

50, 56 .......................................................................................... Protection of Human Subjects and Institutional Review Boards 0910–0130 

601 .............................................................................................. Biologics License Application .................................................... 0910–0338 

803 .............................................................................................. Medical Device Reporting .......................................................... 0910–0437 

‘‘Administrative Procedures for CLIA Categorization’’ and 

‘‘Recommendations: Clinical Laboratory Improvement 

Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices’’.

CLIA Administrative Procedures; CLIA Waivers ....................... 0910–0607 

800, 801, 809, and 830 .............................................................. Medical Device Labeling Requirements; Unique Device Identification.0910–0485 

860 .............................................................................................. Reclassification Petition for Medical Devices ............................ 0910–0138 

‘‘Emergency Use Authorization of Medical Products and Related Authorities’’.EUA ............................................................................................ 0910–0595 

Dated: December 14, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–27852 Filed 12–18–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2023–N–2058] 

James Funaro: Final Debarment Order 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is issuing an 

order under the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) debarring 

James Funaro for a period of 5 years 

from importing or offering for import 

any drug into the United States. FDA 

bases this order on a finding that Mr. 

Funaro was convicted of one felony 

count under Federal law for conspiracy 

to launder money. The factual basis 

supporting Mr. Funaro’s conviction, as 

described below, is conduct relating to 

the importation into the United States of 

a drug or controlled substance. Mr. 

Funaro was given notice of the proposed 

debarment and was given an 

opportunity to request a hearing to show 

why he should not be debarred. As of 

October 11, 2023 (30 days after receipt 

of the notice), Mr. Funaro had not 

responded. Mr. Funaro’s failure to 

respond and request a hearing 

constitutes a waiver of his right to a 

hearing concerning this matter. 

DATES: This order is applicable 

December 19, 2023. 

ADDRESSES: Any application by Mr. 

Funaro for termination of debarment 

under section 306(d)(1) of the FD&C Act 

(21 U.S.C. 335a(d)(1)) may be submitted 

as follows: 

Electronic Submissions 

D Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

An application submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

application will be made public, you are 

solely responsible for ensuring that your 

application does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

application, that information will be 

posted on https://www.regulations.gov. 

D If you want to submit an application 

with confidential information that you 

do not wish to be made available to the 

public, submit the application as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

D Mail/Hand Delivery/Courier (for 

written/paper submissions): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

D For a written/paper application 

submitted to the Dockets Management 

Staff, FDA will post your application, as 

well as any attachments, except for 

information submitted, marked and 

identified, as confidential, if submitted 

as detailed in ‘‘Instructions.’’ 

Instructions: All applications must 

include the Docket No. FDA–2023–N– 

2058. Received applications will be 

placed in the docket and, except for 

those submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 

https://www.regulations.gov or at the 

Dockets Management Staff between 9 

a.m. and 4 p.m., Monday through 

Friday, 240–402–7500. 

D Confidential Submissions—To 

submit an application with confidential 

information that you do not wish to be 

made publicly available, submit your 

application only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of your application. 

The second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. Any information marked as 

‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https:/ 


lotter on DSK11XQN23PROD with NOTICES1